Fig. 2

CLU upregulation reduces parenchymal amyloid accumulation in APP/PS1 mice. a Representative images of fibrillar amyloid deposition in cortex and hippocampus of 8-month-old APP/PS1^AAV-GFP and APP/PS1^AAV-CLU animals. Scale bar, 100 μm. b-c Stereological quantification of (b) fibrillar amyloid deposits (Cortex: APP/PS1^AAV-GFP (0.41 ± 0.05), APP/PS1^AAV-CLU (0.24 ± 0.03); Hippocampus: APP/PS1^AAV-GFP (0.25 ± 0.04), APP/PS1^AAV-CLU (0.11 ± 0.01)) and c total amyloid accumulation (Cortex: APP/PS1^AAV-GFP (0.74 ± 0.06), APP/PS1^AAV-CLU (0.49 ± 0.07); Hippocampus: APP/PS1^AAV-GFP (0.51 ± 0.05), APP/PS1^AAV-CLU (0.29 ± 0.04)), N = 11–12 mice/group. For each animal three brain sections were analyzed. Data are presented as mean ± S.E.M. and each brain region was analyzed by Student’s t, *p < 0.05, **p < 0.01. d Quantification of the Aβ₄₀ and Aβ₄₂ levels in the soluble and insoluble cortical fractions of 8-month-old APP/PS1^AAV-GFP and APP/PS1^AAV-CLU mice by ELISA. N = 10–12 mice/group. Data are presented as mean ± S.E.M.: (soluble Aβ₄₀: APP/PS1^AAV-GFP (1 ± 0.14), APP/PS1^AAV-CLU (0.62 ± 0.09); soluble Aβ₄₂: APP/PS1^AAV-GFP (1 ± 0.18), APP/PS1^AAV-CLU (0.51 ± 0.10)) and insoluble (Aβ₄₀: APP/PS1^AAV-GFP (1 ± 0.21), APP/PS1^AAV-CLU (0.47 ± 0.06); Aβ₄₂: APP/PS1^AAV-GFP (1 ± 0.18), APP/PS1^AAV-CLU (0.56 ± 0.08)). Data analyzed by Student’s t, *p < 0.05. e Amyloid plaques (blue) were surrounded by dystrophic neurites (red) in APP/PS1^AAV-GFP and APP/PS1^AAV-CLU mice. CLU overexpression was associated with overall reduction of neuritic dystrophy in APP/PS1 mice. Scale bar, 100 μm. f Stereological analysis of Lamp1 labeling in cortex and hippocampus of APP/PS1 mice (Cortex: APP/PS1^AAV-GFP (0.73 ± 0.07), APP/PS1^AAV-CLU (0.47 ± 0.06); Hippocampus: APP/PS1^AAV-GFP (0.43 ± 0.05), APP/PS1^AAV-CLU (0.26 ± 0.05)). N = 10 mice/group. Data are presented as mean ± S.E.M. and Student’s t tests were used to analyze cortex and hippocampus, *p < 0.05